The goal of this proposal is to understand the role of the feline retroviruses in naturally occurring leukemias and lymphomas of cats. Specific questions addressed are: (1) Does a particular strain of FeLV account for both the viremia and leukemia observed within multi-cat households that experience abnormally high incidence of FeLV related disease? (2) Is the FeLV genome sufficient to induce disease? (3) Can virus negative lymphomas and leukemias that arise in cats living in FeLV infected environments be attributed to viral infection? (4) What is the region of FeSV that codes for the transformation function? Is FOCMA the product of a transformation gene? Specific aims are: (1) Determination of structural variability of FeLV isolates upon in vivo passage in cats, upon horizontal transmission in laboratory settings, and in the field in multi-cat households. (2) Construction of a recombinant DNA clone of the FeLV pro-virus that is infectious. Test of the ability of FeLV produced by transfection of the cloned DNA to induce leukemia in cats. (3) A search for evidence of FeLV infection in the tumors of non-viremic animals that live in multi-cat households that harbor FeLV infected animals. Specific aims include attempts to isolate infectious FeLV by co-cultivation, induction or transfection from the tumors, to detect FeLV sequences in tumors that are not found in non-tumor tissue, to isolate DNA fragments that code for the transforming activity from the cells.